Daraxonrasib or Chemotherapy in Previously Treated Metastatic Pancreatic Cancer

Authors: Eileen M. O’Reilly, M.D., Zev A. Wainberg, M.D., Andrew E. Hendifar, M.D., Mitesh J. Borad, M.D., Filippo Pietrantonio, M.D., Shubham Pant, M.D., Pascal Hammel, M.D., for the RASolute 302 Trial Investigators

Published May 31, 2026

N Engl J Med 2026;395:325-337

Daraxonrasib is an oral RAS(ON) multiselective, tri-complex inhibitor of the active guanosine triphosphate–bound state of mutant and wild-type RAS.

RESULTS

A total of 500 patients, including 91.8% with RAS G12 mutations, were randomly assigned to receive daraxonrasib (248 patients) or chemotherapy (252 patients). The median overall survival in the RAS G12 population was 13.2 months with daraxonrasib and 6.6 months with chemotherapy, and the median overall survival in the overall population was 13.2 months and 6.7 months, respectively; the hazard ratio was 0.40 in both populations (P<0.001). The median progression-free survival in the RAS G12 population was 7.3 months with daraxonrasib and 3.5 months with chemotherapy, and that in the overall population was 7.2 months and 3.6 months, respectively; the hazard ratios were 0.45 and 0.49, respectively (P<0.001 for both comparisons).

CONCLUSIONS

Among patients with previously treated mPDAC, treatment with daraxonrasib led to significantly longer overall survival and progression-free survival than chemotherapy. Funded by Revolution Medicines; RASolute 302.